Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wild Norway rats (Rattus norvegicus) were collected from a site contaminated by a range of polycyclic aromatic hydrocarbons (PAHs), mineral oils, polychlorobiphenyls (PCBs) and heavy metals. Activities of cytochrome P450 monooxygenases (ethoxy-, pentoxy- and benzoxy-resorufin O-dealkylases, and 4-nitrophenol hydroxylase) were measured in microsomal fractions from liver and lung. Antioxidant enzyme activities (superoxide dismutase, catalase, selenium-dependent and non-selenium-dependent glutathione peroxidases) were also measured in cytosolic fractions from lung and liver, and in erythrocytes. The levels of activities were compared with those found in control laboratory rats and in wild Norway rats reared in a terrarium. Results show that rats living in a polluted environment have monooxygenase activities higher than that of control animals in both liver and lung. Some modifications of antioxidant enzyme activities were also found in these animals.
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PMID:Activities of cytochrome P450-dependent monooxygenases and antioxidant enzymes in different organs of Norway rats (Rattus norvegicus) inhabiting reference and contaminated sites. 857 47

An investigation was made of ethoxyresorufin O-deethylase (EROD) activity, a cytochrome P450 (CYP) dependent enzyme mainly catalyzed by CYP1A1, glutathione S-transferase (GST) activity toward the substrates 1-chloro-2,4- dinitrobenzene (CDNB) and ethacrynic acid (EAA), reduced glutathione (GSH) levels, and antioxidant enzyme (AOE) activity namely catalase (CAT) and selenium- dependent glutathione peroxidase (Se-GPx) in tumor and surrounding tumor-free (normal) tissues in female breast cancer patients. Wide interindividual variations were found in the enzyme activities in both tumor and normal breast tissues. No significant differences were noted between mean EROD and CAT activities in tumor and normal breast tissues. The mean activities of CDNB GST, EAA GST and Se-GPx and GSH levels in tumor tissue were significantly higher than those in normal breast tissue. These results show that CYP, GST and AOE behave differentially in breast tumors.
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PMID:Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue. 1032 33

Previously we have reported that several sesquiterpene lactones isolated from Helenium aromaticum and Telekia speciosa showed pro-oxidative properties and caused glutathione level depletion in rat liver in vivo. In the present study we examined the in vivo effect of these lactones on antioxidant enzyme systems and some drug metabolizing enzymes in the liver and the kidney of rats. We found that the majority of the compounds increased the hepatic activity of glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), but superoxide dismutase (SOD) activity was distinctly lowered by five lactones. A few of the compounds tested caused a decrease in the hepatic cytochrome P450 content and reduced the activity of NADPH-cytochrome P450 reductase, aminopyrine demethylase, aniline hydroxylase and glutathione-S-transferase. Results for the kidney showed fewer changes in activities of both classes of enzymes when compared to the liver. Not all lactones affected the enzymes under test, the most active were: linifolin, helenalin, mexicanin 1 and telekin. 6 alpha-Hydroxy-2,3-dihydroaromaticin behaved differently towards monooxygenases since it induced the activity of aminopyrine demethylase and aniline hydroxylase.
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PMID:Effect of sesquiterpene lactones on antioxidant enzymes and some drug-metabolizing enzymes in rat liver and kidney. 1082 Oct 42

Humics and pesticides are present in aquatic environment and the toxicological consequences of their chemical interaction is well studied. However, data concerning the mechanism of the biochemical action of humic-pesticide combinations are scarce, especially in vertebrates. Thus we have chosen to study the in vivo effects of the plant polyphenolic tannic acid and the pyrethroid insecticide deltamethrin [Decis] alone or in combination on hepatic xenobiotic-metabolizing enzyme activities and the associated redox-parameters in carp, as the complex assessment of these systems are regarded to serve as a relevant biomarker of environmental pollution. Stress effects and tissue damage were followed by determination of the plasma glucose level, the activities of plasma transaminases, and by electron microscopy. Tannic acid alone exerted weak prooxidant effect due to its marked antioxidant enzyme inhibitory activity. Deltamethrin, applied in a very low dose, induced oxyradical production in fish via activation of cytochrome P450 isozymes. This effect was promoted by the antioxidant enzyme inhibitory action of tannic acid, when the two chemicals were combined; however, the ultrastructural damage of the hepatocytes was reduced by the common cytoprotective capacity of the phenolic. Numerous humics are known to alter the toxicity of pesticides and their influence depends on their type and concentration. Therefore, our work taken together with other comparative studies may contribute to the assessment of the impact of humics in nature, especially in case of environmental pollution.
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PMID:Influence of the polyphenolic tannic acid on the toxicity of the insecticide deltametihrin to fish. A comparative study examining both biochemical and cytopathological parameters. 1237 15

Cyclophosphamide (CTX) is in the nitrogen mustard group of alkylating antineoplastic chemotherapeutic agents. It is one of the most frequently used antitumor agents for the treatment of a broad spectrum of human cancers. Thioredoxin reductase (TrxR) catalyze the NADPH-dependent reduction of thioredoxin and play an important role in multiple cellular events related to carcinogenesis including cell proliferation, apoptosis, and cell signaling. This enzyme represents a promising target for the development of cytostatic agents. The purpose of this study is to determine whether CTX could target TrxR in vivo. Lewis lung carcinoma and solid H22 hepatoma treated with 50-250 mg/kg CTX for 3 h lost TrxR activity in a dose-dependent fashion. Over 75% and 95% of TrxR activity was lost at the dose of 250 mg/kg. There was, however, a recovery of TrxR activity such that it attained normal levels by 120 h after a dose of 250 mg/kg. In addition, we found that CTX caused a preferential TrxR inhibition over other antioxidant enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase. We also used ascites H22 cells to investigate cancer cells response after TrxR was inhibited by CTX in vivo since CTX is needed to be activated by liver cytochrome P450 enzymes. The time course and dose-dependent changes of cellular TrxR activity were similar with those in tumor tissue. CTX caused a dose-dependent cellular proliferation inhibition which was positively correlated with TrxR inhibition at 3 h. Furthermore, when 3 h CTX-treated cells with various TrxR backgrounds, harvested from ascites-bearing mice, were implanted into mice, the proliferations of these cells were again proportionally dependent on TrxR activity. The TrxR inhibition could thereby be considered as a crucial mechanism contributing to anticancer effect seen upon clinical use of CTX.
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PMID:Cyclophosphamide as a potent inhibitor of tumor thioredoxin reductase in vivo. 1715 7

In this study, di(2-ethylhexyl)phthalate (DEHP) toxicities to Caenorhabditis elegans were investigated using multiple toxic endpoints, such as mortality, growth, reproduction and stress-related gene expression, focusing on the identification of chemical-induced gene expression as a sensitive biomarker for DEHP monitoring. The possible use of C. elegans as a sentinel organism in the monitoring of soil ecosystem health was also tested by conducting the experiment on the exposure of nematode to field soil. Twenty-four-hour median lethal concentration (LC50) data suggest that DEHP has a relatively high potential of acute toxicity to C. elegans. Decreases in body length and egg number per worm observed after 24h of DEHP exposure may induce long-term alteration in the growth and reproduction of the nematode population. Based on the result from the C. elegans genome array and indicated in the literatures, stress proteins, metallothionein, vitellogenin, xenobiotic metabolism enzymes, apoptosis-related proteins, and antioxidant enzyme genes were selected as stress-related genes and their expression in C. elegans by DEHP exposure was analyzed semi-quantitatively. Expression of heat shock protein (hsp)-16.1 and hsp-16.2 genes was decreased by DEHP exposure. Expression of cytochrome P450 (cyp) 35a2 and glutathione-S-transferease (gst)-4, phase I and phase II of xenobiotic metabolism enzymes, was increased by DEHP exposure in a concentration-dependent manner. An increase in stress-related gene expressions occurred concomitantly with the deterioration on the physiological level, which suggests an increase in expression of those genes may not be considered as a homeostatic response but as a toxicity that might have physiological consequences. The experiment with the soil from the landfill site suggests that the potential of the C. elegans biomarker identified in laboratory conditions should be calibrated and validated for its use in situ.
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PMID:Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans. 1760 95

Intake of ergot alkaloids found in endophyte-infected tall fescue grass is associated with decreased feed intake and reduction in body weight gain. The liver is one of the target organs of fescue toxicosis with upregulation of genes involved in xenobiotic metabolism and downregulation of genes associated with antioxidant pathways. It was hypothesized that short-term exposure of rats to ergot alkaloids would change hepatic cytochrome P450 (CYP) and antioxidant expression, as well as reduce antioxidant enzyme activity and hepatocellular proliferation rates. Hepatic gene expression of various CYPs, selected nuclear receptors associated with the CYP induction, and antioxidant enzymes were measured using real-time PCR. Hepatic expression of CYP, antioxidant and proliferating cell nuclear antigen (PCNA) proteins were measured using Western blots. The CYP3A1 protein expression was evaluated using primary rat hepatocellular cultures treated with ergovaline, one of the major ergot alkaloids produced by fescue endophyte, in order to assess the direct role of ergot alkaloids in CYP induction. The enzyme activities of selected antioxidants were assayed spectrophotometrically. While hepatic CYP and nuclear receptor expression were increased in ergot alkaloid-exposed rats, the expression and activity of antioxidant enzymes were reduced. This could potentially lead to increased oxidative stress, which might be responsible for the decrease in hepatocellular proliferation after ergot alkaloid exposure. This study demonstrated that even short-term exposure to ergot alkaloids can potentially induce hepatic oxidative stress which can contribute to the pathogenesis of fescue toxicosis.
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PMID:Effect of ergot alkaloids associated with fescue toxicosis on hepatic cytochrome P450 and antioxidant proteins. 1820 39

The aim of this study was to evaluate the effects of the administration of pregnenolone-16alpha-carbonitrile (PCN), an inducer of the cytochrome P450 3A gene in rats, on vitamin E status and antioxidant enzyme protein levels in rats fed a vitamin E-supplemented diet. Two groups of male Wistar rats were fed for 3 weeks with a basal diet containing 50 ppm of alpha-tocopherol or the same diet containing 10 times more alpha-tocopherol. In the final 3 days, each group was divided into two subgroups which were given a single daily intraperitoneal injection of PCN at 75 mg/kg (groups PCN and PCN+VE) or DMSO (groups DS and DS+VE). PCN treatment alone significantly reduced the alpha-tocopherol content of the liver and plasma and this effect was prevented by supplementation with 10-fold more alpha-tocopherol. alpha-Tocopherol levels in the kidneys, lung, heart, and testes were significantly higher in both vitamin E-supplemented groups than in the control groups. TBARS levels in the liver and lung were significantly increased in both PCN-treated groups, as shown by two-way ANOVA analysis. PCN also caused a significant reduction in protein levels of catalase and glutathione peroxidase (GPx) in both groups. Dietary vitamin E supplementation caused a decrease in liver protein levels of GPx and superoxide dismutase, but not catalase, in both groups and protected against PCN-induced lipid peroxidation, which was caused by CYP3A induction and a reduction in antioxidant enzyme levels.
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PMID:Effects of pregnenolone-16alpha-carbonitrile on vitamin E status and protein levels of antioxidant enzymes in male rats fed a vitamin E-supplemented diet. 1938 73

Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for 5 d. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sublethal toxicity, as well as illuminate possible causative agents.
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PMID:Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P450 1A activity, and plasma phosphate in fish. 1961 Jun 78

Present study was undertaken to investigate if short-term UV-B (4.2 kJ m(-2) day(-1)) and UV-C (5.7 kJ m(-2) day(-1)), pre-treatments can induce artemisinin biosynthesis in Artemisia annua. Twenty-one day old Artemisia seedlings were subjected to short-term (14 days) UV pre-treatment in an environmentally controlled growth chamber and then transplanted to the field under natural conditions. Treatment of A. annua with artificial UV-B and UV-C radiation not only altered the growth responses, biomass, pigment content and antioxidant enzyme activity but enhanced the secondary metabolites (artemisinin and flavonoid) content at all developmental stages as compared to non-irradiated plants. The extent of oxidative damage was measured in terms of the activities of enzymes such as catalase, superoxide dismutase and ascorbate peroxidase. Reinforcement in the antioxidative defense system seems to be a positive response of plants in ameliorating the negative effects of UV-B and UV-C radiations. While the carotenoid content was elevated, the chlorophyll content decreased under UV-B and UV-C pre-treatments. The reverse transcription PCR analysis of the genes associated in artemisinin/isoprenoid biosynthesis like 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), cytochrome P450 oxidoreductase (CPR) and amorpha-4,11-diene synthase (ADS) genes at different growth stages revealed UV induced significant over-expression of the above protein genes. UV-B and UV-C pre-treatments, led to an increase in the concentrations of artemisinin at full bloom stage by 10.5% and 15.7% than that of the control respectively. Thus, the result of our study suggests that short term UV-B pre-treatment of seedlings in greenhouse prior to transplantation into the field enhances artemisinin production with lesser yield related damages as compared to UV-C radiation in A. annua.
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PMID:UV-B and UV-C pre-treatments induce physiological changes and artemisinin biosynthesis in Artemisia annua L. - an antimalarial plant. 2201 53


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